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Effects of DCK knockdown on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells

Abstract

The present study explored the effect that deoxycytidine kinase (DCK) knockdown had on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells. Human cervical cancer HeLa cells that had received no prior treatment were selected from the HeLa group. The HeLa-negative control (NC) group consisted of cells that had undergone an empty vector treatment, and finally the HeLa-short hairpin RNA (shRNA) group included cells that were treated by means of shRNA-DCK expression. DCK expressions were evaluated by quantitative real-time polymerase chain reaction in addition to western blotting assays. Cell proliferation was estimated using the Cell Counting Kit-8 (CCK-8) assay and cell cycle progression. Cell apoptosis was determined by flow cytometry. BALB/c nude mice (n=24) were selected to establish transplanted tumor models, with gross tumor volume measured every 3 days. The results in vitro were as follows: compared with the HeLa group, the HeLa-shRNA group exhibited downregulation of DCK expression and inhibition of cell proliferation at 48, 72 and 96 h. Additionally, more cells in the HeLa-shRNA group were arrested in G0/G1 stage and less in S and G2/M stages, as well as in promotion of cell apoptosis. In vivo results are as follows: when comparing the HeLa and HeLa-NC groups, the gross tumor volume of the transplanted tumor in nude mice in the HeLa-shRNA group was found to have decreased in 13, 16, 19 and 22 days. Based on these findings, our study suggests that DCK knockdown facilitates apoptosis while inhibiting proliferation and tumorigenicity in vivo of cervical cancer HeLa cells.

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References

  1. Meijer CJ, Snijders PJ . Cervical cancer in 2013: screening comes of age and treatment progress continues. Nat Rev Clin Oncol 2014; 11: 77–78.

    Article  CAS  Google Scholar 

  2. Ellenson LH, Wu TC . Focus on endometrial and cervical cancer. Cancer Cell 2004; 5: 533–538.

    Article  CAS  Google Scholar 

  3. Vaccarella S, Lortet-Tieulent J, Plummer M, Franceschi S, Bray F . Worldwide trends in cervical cancer incidence: impact of screening against changes in disease risk factors. Eur J Cancer 2013; 49: 3262–3273.

    Article  Google Scholar 

  4. Frazer IH . Prevention of cervical cancer through papillomavirus vaccination. Nat Rev Immunol 2004; 4: 46–54.

    Article  CAS  Google Scholar 

  5. Janicek MF, Averette HE . Cervical cancer: prevention, diagnosis, and therapeutics. CA Cancer J Clin 2001; 51: 92–114; quiz 115–118.

    Article  CAS  Google Scholar 

  6. Garima PS, Pandey LK, Saxena AK, Patel N . The role of p53 gene in cervical carcinogenesis. J Obstet Gynaecol India 2016; 66: 383–388.

    Article  CAS  Google Scholar 

  7. Gupta A, Ahmad MK, Mahndi AA, Singh R, Pradeep Y . Promoter methylation and relative mRNA expression of the p16 gene in cervical cancer in North Indians. Asian Pac J Cancer Prev 2016; 17: 4149–4154.

    Article  Google Scholar 

  8. Toy G, Austin WR, Liao HI, Cheng D, Singh A, Campbell DO et al. Requirement for deoxycytidine kinase in T and B lymphocyte development. Proc Natl Acad Sci USA 2010; 107: 5551–5556.

    Article  CAS  Google Scholar 

  9. Ferrandina G, Mey V, Nannizzi S, Ricciardi S, Petrillo M, Ferlini C et al. Expression of nucleoside transporters, deoxycitidine kinase, ribonucleotide reductase regulatory subunits, and gemcitabine catabolic enzymes in primary ovarian cancer. Cancer Chemother Pharmacol 2010; 65: 679–686.

    Article  CAS  Google Scholar 

  10. Hubeek I, Stam RW, Peters GJ, Broekhuizen R, Meijerink JP, van Wering ER et al. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia. Br J Cancer 2005; 93: 1388–1394.

    Article  CAS  Google Scholar 

  11. Geutjes EJ, Tian S, Roepman P, Bernards R . Deoxycytidine kinase is overexpressed in poor outcome breast cancer and determines responsiveness to nucleoside analogs. Breast Cancer Res Treat 2012; 131: 809–818.

    Article  CAS  Google Scholar 

  12. Shi JY, Shi ZZ, Zhang SJ, Zhu YM, Gu BW, Li G et al. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients. Pharmacogenetics 2004; 14: 759–768.

    Article  CAS  Google Scholar 

  13. Bunimovich YL, Nair-Gill E, Riedinger M, McCracken MN, Cheng D, McLaughlin J et al. Deoxycytidine kinase augments ATM-mediated DNA repair and contributes to radiation resistance. PLoS ONE 2014; 9: e104125.

    Article  Google Scholar 

  14. Tinoco ML, Dias BB, Dall'Astta RC, Pamphile JA, Aragao FJ . In vivo trans-specific gene silencing in fungal cells by in planta expression of a double-stranded RNA. BMC Biol 2010; 8: 27.

    Article  Google Scholar 

  15. Zhou WJ, Zhang C, Liu Y, Liu P, Ma M, Zhang SF . Influence of oxidative stress on apoptosis and expression of bax and bcl-2 of enterocytes in burn rats with delayed resuscitation on the plateau. Zhonghua Shao Shang Za Zhi 2009; 25: 289–293.

    PubMed  Google Scholar 

  16. Tjalma WA, Weyler JJ, Bogers JJ, Pollefliet C, Baay M, Goovaerts GC et al. The importance of biological factors (bcl-2, bax, p53, PCNA, MI, HPV and angiogenesis) in invasive cervical cancer. Eur J Obstet Gynecol Reprod Biol 2001; 97: 223–230.

    Article  CAS  Google Scholar 

  17. Lv GF, Shi HW, Fan L, Feng ZM, Wang GY . Intensive insulin treatment protected the cardiac myocytes against apoptosis in severely scalded rats. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2011; 23: 714–717.

    PubMed  Google Scholar 

  18. Fan W, Zhou ZY, Huang XF, Bao CD, Du F . Deoxycytidine kinase promotes the migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis patients. Int J Clin Exp Pathol 2013; 6: 2733–2744.

    PubMed  PubMed Central  Google Scholar 

  19. Balakrishnan K, Nimmanapalli R, Ravandi F, Keating MJ, Gandhi V . Forodesine, an inhibitor of purine nucleoside phosphorylase, induces apoptosis in chronic lymphocytic leukemia cells. Blood 2006; 108: 2392–2398.

    Article  CAS  Google Scholar 

  20. Wang HY, Yu HZ, Huang SM, Zheng YL . p53, Bcl-2 and cox-2 are involved in berberine hydrochloride-induced apoptosis of HeLa229 cells. Mol Med Rep 2016; 14: 3855–3861.

    Article  CAS  Google Scholar 

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Acknowledgements

We appreciate the reviewers for their helpful comments.

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Correspondence to H-R Gao.

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Shang, QY., Wu, CS. & Gao, HR. Effects of DCK knockdown on proliferation, apoptosis and tumorigenicity in vivo of cervical cancer HeLa cells. Cancer Gene Ther 24, 367–372 (2017). https://doi.org/10.1038/cgt.2017.31

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